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6nxf

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Crystal structure of mouse REC114 PH domain in complex with ANKRD31 C terminus

Structural highlights

6nxf is a 4 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.791Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RE114_MOUSE Required for DNA double-strand breaks (DSBs) formation in unsynapsed regions during meiotic recombination (PubMed:20551173, PubMed:27723721). Probably acts by forming a complex with IHO1/CCDC36 and MEI4, which activates DSBs formation in unsynapsed regions, an essential step to ensure completion of synapsis (PubMed:27723721).^[1] ^[2]

Publication Abstract from PubMed

Double-strand breaks (DSBs) initiate the homologous recombination that is crucial for meiotic chromosome pairing and segregation. Here, we unveil mouse ANKRD31 as a lynchpin governing multiple aspects of DSB formation. Spermatocytes lacking ANKRD31 have altered DSB locations and fail to target DSBs to the pseudoautosomal regions (PARs) of sex chromosomes. They also have delayed and/or fewer recombination sites but, paradoxically, more DSBs, suggesting DSB dysregulation. Unrepaired DSBs and pairing failures-stochastic on autosomes, nearly absolute on X and Y-cause meiotic arrest and sterility in males. Ankrd31-deficient females have reduced oocyte reserves. A crystal structure defines a pleckstrin homology (PH) domain in REC114 and its direct intermolecular contacts with ANKRD31. In vivo, ANKRD31 stabilizes REC114 association with the PAR and elsewhere. Our findings inform a model in which ANKRD31 is a scaffold anchoring REC114 and other factors to specific genomic locations, thereby regulating DSB formation.

REC114 Partner ANKRD31 Controls Number, Timing, and Location of Meiotic DNA Breaks.,Boekhout M, Karasu ME, Wang J, Acquaviva L, Pratto F, Brick K, Eng DY, Xu J, Camerini-Otero RD, Patel DJ, Keeney S Mol Cell. 2019 Apr 11. pii: S1097-2765(19)30227-8. doi:, 10.1016/j.molcel.2019.03.023. PMID:31003867^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kumar R, Bourbon HM, de Massy B. Functional conservation of Mei4 for meiotic DNA double-strand break formation from yeasts to mice. Genes Dev. 2010 Jun 15;24(12):1266-80. doi: 10.1101/gad.571710. PMID:20551173 doi:http://dx.doi.org/10.1101/gad.571710
↑ Stanzione M, Baumann M, Papanikos F, Dereli I, Lange J, Ramlal A, Trankner D, Shibuya H, de Massy B, Watanabe Y, Jasin M, Keeney S, Toth A. Meiotic DNA break formation requires the unsynapsed chromosome axis-binding protein IHO1 (CCDC36) in mice. Nat Cell Biol. 2016 Nov;18(11):1208-1220. doi: 10.1038/ncb3417. Epub 2016 Oct 10. PMID:27723721 doi:http://dx.doi.org/10.1038/ncb3417
↑ Boekhout M, Karasu ME, Wang J, Acquaviva L, Pratto F, Brick K, Eng DY, Xu J, Camerini-Otero RD, Patel DJ, Keeney S. REC114 Partner ANKRD31 Controls Number, Timing, and Location of Meiotic DNA Breaks. Mol Cell. 2019 Apr 11. pii: S1097-2765(19)30227-8. doi:, 10.1016/j.molcel.2019.03.023. PMID:31003867 doi:http://dx.doi.org/10.1016/j.molcel.2019.03.023